tbuckley/cabot-search huggingface dataset:
Reprogramming Cancer into Antigen-Presenting Cells as a Novel Immunotherapy
Authors: Miles H. Linde, Amy C. Fan, Thomas Köhnke, Aaron C. Trotman-Grant, Sarah F. Gurev, Paul Phan, Feifei Zhao, Naomi L. Haddock, Kevin A. Nuno, Eric J. Gars, Melissa Stafford, Payton L. Marshall, Christopher G. Dove, Ian L. Linde, Niklas Landberg, Lindsay P. Miller, Robbie G. Majzner, Tian Yi Zhang, Ravindra Majeti
Journal: Cancer Discovery (2023)

Therapeutic cancer vaccination seeks to elicit activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAA) and eradicating malignant cells. Here, we present a cancer vaccination approach utilizing myeloid-lineage reprogramming to directly convert cancer cells into tumor-reprogrammed antigen-presenting cells (TR-APC). Using syngeneic murine leukemia models, we demonstrate that TR-APCs acquire both myeloid phenotype and function, process and present endogenous TAAs, and potently stimulate TAA-specific CD4+ and CD8+ T cells. In vivo TR-APC induction elicits clonal expansion of cancer-specific T cells, establishes cancer-specific immune memory, and ultimately promotes leukemia eradication. We further show that both hematologic cancers and solid tumors, including sarcomas and carcinomas, are amenable to myeloid-lineage reprogramming into TR-APCs. Finally, we demonstrate the clinical applicability of this approach by generating TR-APCs from primary clinical specimens and stimulating autologous patient-derived T cells. Thus, TR-APCs represent a cancer vaccination therapeutic strategy with broad implications for clinical immuno-oncology. Despite recent advances, the clinical benefit provided by cancer vaccination remains limited. We present a cancer vaccination approach leveraging myeloid-lineage reprogramming of cancer cells into APCs, which subsequently activate anticancer immunity through presentation of self-derived cancer antigens. Both hematologic and solid malignancies derive significant therapeutic benefit from reprogramming-based immunotherapy. This article is highlighted in the In This Issue feature, p. 1027.
A Call to Action to Improve Outcomes in Women Undergoing Surgical Coronary Revascularization
Authors: Brittany A. Zwischenberger, Jennifer S. Lawton
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Characterizing Epidemiology and Burden of Disease in Alopecia Areata—Making It Count
Authors: Amy J. McMichael, Mya L. Roberson
Journal: JAMA Dermatology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
CeDAR: incorporating cell type hierarchy improves cell type-specific differential analyses in bulk omics data
Authors: Luxiao Chen, Ziyi Li, Hao Wu
Journal: Genome biology (2023)

Bulk high-throughput omics data contain signals from a mixture of cell types. Recent developments of deconvolution methods facilitate cell type-specific inferences from bulk data. Our real data exploration suggests that differential expression or methylation status is often correlated among cell types. Based on this observation, we develop a novel statistical method named CeDAR to incorporate the cell type hierarchy in cell type-specific differential analyses of bulk data. Extensive simulation and real data analyses demonstrate that this approach significantly improves the accuracy and power in detecting cell type-specific differential signals compared with existing methods, especially in low-abundance cell types.
Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer
Authors: Chaofan Liu, Xi Wang, Wan Qin, Jingyao Tu, Chunya Li, Weiheng Zhao, Li Ma, Bo Liu, Hong Qiu, Xianglin Yuan
Journal: Cancer Communications (2023)

Abstract Background Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) have shown a moderate response in colorectal cancer (CRC) with deficient mismatch repair (dMMR) functions and poor response in patients with proficient MMR (pMMR). pMMR tumors are generally immunogenically “cold”, emphasizing combination strategies to turn the “cold” tumor “hot” to enhance the efficacy of ICIs. ATR inhibitors (ATRi) have been proven to cooperate with radiation to promote antitumor immunity, but it is unclear whether ATRi could facilitate the efficacy of IR and ICI combinations in CRCs. This study aimed to investigate the efficacy of combining ATRi, irradiation (IR), and anti‐PD‐L1 antibodies in CRC mouse models with different microsatellite statuses. Methods The efficacy of combining ATRi, IR, and anti‐PD‐L1 antibodies was evaluated in CRC tumors. The tumor microenvironment and transcriptome signatures were investigated under different treatment regimens. The mechanisms were explored via cell viability assay, flow cytometry, immunofluorescence, immunoblotting, co‐immunoprecipitation, and real‐time quantitative PCR in multiple murine and human CRC cell lines. Results Combining ATRi berzosertib and IR enhanced CD8 + T cell infiltration and enhanced the efficacy of anti‐PD‐L1 therapy in mouse CRC models with different microsatellite statuses. The mechanistic study demonstrated that IR + ATRi could activate both the canonical cGAS‐STING‐pTBK1/pIRF3 axis by increasing cytosolic double‐stranded DNA levels and the non‐canonical STING signaling by attenuating SHP1‐mediated inhibition of the TRAF6‐STING‐p65 axis, via promoting SUMOylation of SHP1 at lysine 127. By boosting the STING signaling, IR + ATRi induced type I interferon‐related gene expression and strong innate immune activation and reinvigorated the cold tumor microenvironment, thus facilitating immunotherapy. Conclusions The combination of ATRi and IR could facilitate anti‐PD‐L1 therapy by promoting STING signaling in CRC models with different microsatellite statuses. The new combination strategy raised by our study is worth investigating in the management of CRC.
Do Thiazides Reduce the Risk of Kidney-Stone Recurrence?
Authors: R. Todd Alexander
Journal: New England Journal of Medicine (2023)

Kidney stones have plagued humanity for millennia. Unfortunately, the prevalence of this common, costly, and painful condition is increasing, as is the list of associated coexisting disorders that includes hypertension, diabetes, obesity, dyslipidemia, and, more recently, cardiovascular and kidney disease.1,2 The incidence of stone recurrence is high; unfortunately, there have been no new treatments for the prevention of recurrence of kidney stones in decades. Current initial treatment focuses on dietary interventions. However, these often fail to prevent the recurrence of stones, which results in the need for medical therapy, and the drug class that is best supported with evidence is . . .
ADHD Drugs in Pregnancy Not Linked to Children’s Brain Development
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Novel Ubiquitin Complex Regulates Aneuploid Epithelial Tumors by Moderating an Integrated Stress Response
Authors: Nektaria Maria Leli, Constantinos Koumenis
Journal: Cancer Discovery (2023)

Tumor fitness coessentiality gene analysis that aims to expand the repertoire of druggable targets reveals a novel ubiquitin ligase complex, the BICR6 module. Along with the other complex members (UBA6, KCMF1, and UBR4), BIRC6 selectively contributes to the survival of a subset of epithelial tumors with a high degree of aneuploidy by ubiquitinating and suppressing HRI, a component of the integrated stress response adaptive pathway. See related article by Cervia et al., p. 766 (2).
correctKin: an optimized method to infer relatedness up to the 4th degree from low-coverage ancient human genomes
Authors: Emil Nyerki, Tibor Kalmár, Oszkár Schütz, Rui M. Lima, Endre Neparáczki, Tibor Török, Zoltán Maróti
Journal: Genome biology (2023)

Abstract Kinship analysis from very low-coverage ancient sequences has been possible up to the second degree with large uncertainties. We propose a new, accurate, and fast method, correctKin, to estimate the kinship coefficient and the confidence interval using low-coverage ancient data. We perform simulations and also validate correctKin on experimental modern and ancient data with widely different genome coverages (0.12×–11.9×) using samples with known family relations and known/unknown population structure. Based on our results, correctKin allows for the reliable identification of relatedness up to the 4th degree from variable/low-coverage ancient or badly degraded forensic whole genome sequencing data.
Colorectal cancer statistics, 2023
Authors: Rebecca L. Siegel, Nikita Sandeep Wagle, Andrea Cercek, Robert A. Smith, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2023)

Abstract Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC statistics based on incidence from population‐based cancer registries and mortality from the National Center for Health Statistics. In 2023, approximately 153,020 individuals will be diagnosed with CRC and 52,550 will die from the disease, including 19,550 cases and 3750 deaths in individuals younger than 50 years. The decline in CRC incidence slowed from 3%–4% annually during the 2000s to 1% annually during 2011–2019, driven partly by an increase in individuals younger than 55 years of 1%–2% annually since the mid‐1990s. Consequently, the proportion of cases among those younger than 55 years increased from 11% in 1995 to 20% in 2019. Incidence since circa 2010 increased in those younger than 65 years for regional‐stage disease by about 2%–3% annually and for distant‐stage disease by 0.5%–3% annually, reversing the overall shift to earlier stage diagnosis that occurred during 1995 through 2005. For example, 60% of all new cases were advanced in 2019 versus 52% in the mid‐2000s and 57% in 1995, before widespread screening. There is also a shift to left‐sided tumors, with the proportion of rectal cancer increasing from 27% in 1995 to 31% in 2019. CRC mortality declined by 2% annually from 2011–2020 overall but increased by 0.5%–3% annually in individuals younger than 50 years and in Native Americans younger than 65 years. In summary, despite continued overall declines, CRC is rapidly shifting to diagnosis at a younger age, at a more advanced stage, and in the left colon/rectum. Progress against CRC could be accelerated by uncovering the etiology of rising incidence in generations born since 1950 and increasing access to high‐quality screening and treatment among all populations, especially Native Americans.
Skin-Cancer Chemoprevention in Transplant Recipients
Authors: David M. Miller, Kevin S. Emerick
Journal: New England Journal of Medicine (2023)

Keratinocyte carcinomas include squamous-cell carcinoma of the skin and basal-cell carcinoma and are the predominant forms of nonmelanoma skin cancer. Keratinocyte carcinomas are the most common cancer in humans, with an annual incidence greater than all other cancers combined.1,2 Whereas the vast majority of basal-cell and squamous-cell carcinomas are cured with local destruction or surgical excision, treatment of keratinocyte carcinomas can lead to considerable morbidity and health care–related economic burden. Furthermore, a subgroup of patients with nonmelanoma skin cancers have poor outcomes, including recurrence, metastases, and death. Owing to the sheer number of keratinocyte carcinomas that are diagnosed each year, . . .
On-Demand Male Contraceptive Compound Promising in Mouse Study
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hard to Swallow
Authors: Debra Malina, Mridula Nadamuni, Lisa Rosenbaum, Caren Solomon, Timothy Vining
Journal: New England Journal of Medicine (2023)

This short Double Take video from the New England Journal of Medicine emphasizes the importance of remaining vigilant in broadening the differential diagnosis when clinical cases evolve atypically. Focusing on a patient whose diagnosis was delayed, the video guides viewers through the sequential clinical events that required additional diagnostic evaluation, culminating in the final diagnosis. This video is based on a Clinical Problem-Solving article published in the Journal (Hard to Swallow, by M.J. Litt et al., in the October 7, 2021, issue), and the companion Interactive Medical Case (in the September 30, 2021, issue).
Highlights From CROI, the Conference on Retroviruses and Opportunistic Infections—Postexposure Prophylaxis for Sexually Transmitted Infections, a New Protease Inhibitor for COVID-19, Goals for Preventing HIV Transmission, and More
Authors: Rita Rubin
Journal: JAMA (2023)

This Medical News Q&A discusses research highlights from the recent Conference on Retroviruses and Opportunistic Infections.
Myocardial Metabolomics of Human Heart Failure With Preserved Ejection Fraction
Authors: Virginia S. Hahn, Christopher Petucci, Min-Soo Kim, Kenneth C. Bedi, Hanghang Wang, Sumita Mishra, Navid Koleini, Edwin J. Yoo, Kenneth B. Margulies, Zoltan Arany, Daniel P. Kelly, David A. Kass, Kavita Sharma
Journal: Circulation (2023)

The human heart primarily metabolizes fatty acids, and this decreases as alternative fuel use rises in heart failure with reduced ejection fraction (HFrEF). Patients with severe obesity and diabetes are thought to have increased myocardial fatty acid metabolism, but whether this is found in those who also have heart failure with preserved ejection fraction (HFpEF) is unknown.
Using Diffuse Reflectance Spectroscopy to Classify Tumor Tissue in Upper Gastrointestinal Cancers
Authors: Yi-Xin Liu, Yu-Shang Yang
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Overall and Racial and Ethnic Subgroup Prevalences of Alopecia Areata, Alopecia Totalis, and Alopecia Universalis
Authors: Nene Sy, Nicole Mastacouris, Andrew Strunk, Amit Garg
Journal: JAMA Dermatology (2023)

Importance Prevalences of alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) are poorly established. Objective To estimate overall and subgroup prevalences of AA and its subtypes. Design, Setting, and Participants This cross-sectional study using electronic records comprising the Explorys database (Watson Health, IBM Corporation) included children, adolescents, and adults seeking healthcare across the 4 census regions in the US between January 1, 2019, and December 31, 2019. The statistical analysis was conducted between July 21, 2022, and December 22, 2022. Main Outcomes and Measures Prevalent cases of AA, AT, and AU. Results Of the 1 093 176 patients who met inclusion criteria, 1812 had at least 1 code for AA, 1216 female (67%) and 596 male (33%) patients. Overall age-and-sex standardized prevalences among adults and among children and adolescents were observed to be 0.18% and 0.10%, respectively. The age-standardized prevalence ratio in women to men was 1.32. Standardized prevalence was highest in those aged 30 to 39 (297 per 100 000; 95% CI, 263-335) and 40 to 49 (270 per 100 000; 95% CI, 240-303) years. The highest standardized prevalence was observed among Asian patients (414 per 100 000; 95% CI, 306-548), followed by patients reporting another race or multiple races (314 per 100 000; 95% CI, 266-368), Black (226 per 100 000; 95% CI, 199-255), and Hispanic/Latino (212 per 100 000; 95% CI, 129-328) patients. White patients had the lowest standardized prevalence (168 per 100 000; 95% CI, 157-179) among racial and ethnic subgroups. Relative to White patients, standardized prevalence ratios for Asian, Black, and Hispanic/Latino patients were 2.47 (95% CI, 2.17-2.81), 1.35 (95% CI, 1.26-1.44), and 1.26 (95% CI, 1.03-1.55), respectively. Cases of AT and AU comprised approximately 9% of patients diagnosed with AA. Conclusions and Relevance The findings of this cross-sectional study suggest that there is a significant burden of AA, AT, and AU in the US in which people of color, particularly Asian Americans, appear to be disproportionately affected.
Nadofaragene Firadenovec: First Approval
Authors: Arnold Lee
Journal: Drugs (2023)

Nadofaragene firadenovec (nadofaragene firadenovec-vncg; Adstiladrin®) is a non-replicating adenoviral vector-based gene therapy developed by Ferring Pharmaceuticals for the treatment of high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC). Nadofaragene firadenovec constitutes vector DNA that encodes for interferon (IFN)-α2b and is the first approved gene therapy in bladder cancer. The production of IFN-α2b by transfected urothelial cells is associated with anticancer activity, including immunostimulatory, antiangiogenic and apoptotic effects. In December 2022, nadofaragene firadenovec received its first global approval in the USA for the treatment of high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumours in adults. This article summarizes the milestones in the development of nadofaragene firadenovec leading to this first approval for this indication.
Chronic Pain at Multiple Sites Tied to Increased Dementia Risk
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal